Yes, it can be brutal
I did San Jose to the New Jersey side of Philadelphia for a year and a half. My schedule was generally 2 weeks there and two weeks home.
I would do SJC-PHL via MSP on Sunday. The flight left about 12:30 PM and I would get into PHL about 10:30. I would take a Rapid Rover shuttle to my boss' house and pick up the car and then travel for an hour to the hotel that I stayed in. The goal was to be in the room by 1AM. Monday morning was no fun.
Going home the following Friday was either leave around 1PM and get into SJC about 7:30 or stay until 4 and get in at 11.
I kept a full set of clothes in New Jersey; packed in a large suitcase. Thursday before leaving I would drop my laundry off and a laundromat that washed and folded by the pound. Even without factoring in the time necessary to do it myself, it was cheaper that way. I would pick them up Friday morning, repack the clean clothes, check out of the hotel and have someone drop me off at the airport (or take the shuttle).
I found that I was always in one of two modes. I was either in New Jersey or getting ready to go to New Jersey. Note that there was never a time when I felt at home.
My wife and I became individually more independent. My oldest was in college and was least effected. My youngest was in high school and he and his mother are probably closer even now, 6 years later, than they would be otherwise.
Some of the independence was a good thing but we collectively ran the check book into the ditch more than once. I found that I was planned into, or out of, things without my knowledge.
Being 3 time zones out of sync has the obvious problems. Jet lag; 9-12 time zones/month keeps your internal clock always wrong. Having a cell phone from home means that you will get the occasional 2AM call that starts with "were you asleep?"
Eating is a problem. You will eat out too much when you are away and not want to eat out when you are home. You will eat the wrong foods in inappropriate quantities. Eating becomes a chore. Dining alone is the rule, not the exception.
A noise cancelling headset is a must.
I was frustrated that I wasn't flying enough (on one carrier) to get status but enough that the Skycap knew where I was going before I told him.
In all of the trips, I only remember a couple of weather or mechanical problems that significantly impaired a trip. I ended up in Las Vegas at 2AM rather than home at 11 once but, that was the only time that I had to get a hotel room on the road. I don't count getting into SFO or OAK rather than SJC as a significant diversion.
The challenges that life has are magnified. If you get sick, you have a 50-50 chance that it will be while you are away unless you know Murphy; then you have a 100% chance of being sick on the road. Death in the family? Works the same way. Getting into DIA after midnight to a no room in the inn situation only makes a bad day longer. It really couldn't get worse.
When it came to an end, it was my decision. I finally could not do it any more and that realization came almost over night. I took a job that I initially turned down a couple of months earlier, clipped my wings and only travel occasionally now.
One other thing. The only thing that I regretted was that I worked almost every weekend. I somehow thought that the amount of work was finite and that by working those days I would get ahead of things. I know, sounds dumb even now. I really wish that I had taken the time to take in some of the fun things on the east coast. NYC and Washington DC were only a couple of hours away and yet, I never went. Don't make that mistake.
Lynn